Co-inoculation of tumorigenic rat prostate mesenchymal cells with non-tumorigenic epithelial cells results in the development of carcinosarcoma in syngeneic and athymic animals (original) (raw)
Related papers
Isolation, culture and characterization of epithelial cells derived from rat ventral prostate
The Anatomical record, 1980
Epithelial-cell enriched primary cultures have been established from rat ventral prostate (RVP). Minced ventral prostates were dissociated with 0.5% collagenase in F12K tissue culture medium containing 1% fetal bovine serum. This treatment resulted in the gradual removal of stromal elements from the base of the epithelial cells. After 60 minutes of digestion the aggregates of epithelial cells were washed and plated at high density in F12K plus 10% horse serum. After 48 hours in vitro the unattached cells were removed from the culture dishes, washed, and reinoculated into new culture vessels containing fresh medium. After 96 hours in vitro, the aggregates had attached to the culture vessels and spread out to yield discrete patches of epithelial cells. By 144 hours in vitro the patches of cells had grown and coalesced to form a semi-confluent monolayer of epithelial cells. Ultrastructrual examination of these cultures indicated that adjacent cells were joined by desmosomes and tight j...
Cancer research, 1994
We have established two new epithelial cell lines (NRP-152, NRP-154), with markedly different properties, from the dorsal-lateral prostate of Lobund/Wistar rats treated with N-methyl-N-nitrosourea and testosterone propionate. NRP-152 cells do not form tumors in athymic mice and retain many of the properties of normal prostatic epithelial cells. They produce prostatic acid phosphatase, have functional androgen receptors, and require the combination of several growth factors in addition to serum for optimal growth. Their growth is stimulated by epidermal growth factor, insulin, dexamethasone, cholera toxin, dihydrotestosterone, and testosterone, and their growth is inhibited by transforming growth factor beta s and retinoic acid. These cells also respond to 1,25-dihydroxyvitamin D3 with an early growth stimulation followed by growth inhibition at later times. In contrast, tumorigenic NRP-154 cells lack detectable androgen receptor mRNA and have less stringent growth factor requirement...
Normal and benign human prostatic epithelium in culture
In Vitro, 1979
Isolation of normal human glandular epithelia and their growth and maintenance in vitro have been major problems. The primary objective of studies presented here was to isolate postpubertal, normal human, viable prostatic epithelium for in vitro cultivation. The long-term objective of these investigations was to develop an in vitro human cell model system for studies on prostatic carcinogenesis. A method for isolation of viable, normal and benign human prostatic epithelium, using collagenase for tissue dissociation, is described. Intact acini were isolated, which, on plating gave rise to vigorously growing monolayer cultures of epithelial cells. The purity of epithelial cultures partly depended upon the source of tissue. Specimens of normal prostate and those of benign tissue derived from open prostatectomies provided primarily pure epithelial cultures with occasional fibroblast colonies in some cultures, which could be removed. Cultures from some specimens of transurethral resection of the prostate (TURPD contained many fibroblast colonies due to incomplete separation of acini from the stroma. This resulted from incomplete digestion of denatured tissue caused by electrocauterization during surgery. Cultures established in this manner are being used to study the effects of hormones, vitamins and other growth regulators in order to establish growth requirements of these cells in vitro, which would facilitate their long-term maintenance.
advanced prostatic intraepithelial neoplasia (PIN) (1,2). These abnormalities are associated with a loss, decrease or altered these proteins is critical for normal morphogenesis. The aim of this study was to establish three-dimensional (3-D) in vitro Invasive prostatic carcinomas and prostatic intraepithelial cell models, derived from non-tumorigenic and tumorigenic neoplasia (PIN) are characterized by a loss of normal cell human prostatic epithelial cells, which could be used to organization, cell polarity, and cell:cell and cell:basement investigate mechanisms involved in acinar morphogenesis membrane adhesion. The objective of this study was to and differentiation in both normal and malignant prostatic establish in vitro three-dimensional (3-D) cell models which can be used to investigate mechanisms involved in acinar epithelium.
Malignant transformation in a nontumorigenic human prostatic epithelial cell line
Cancer research, 2001
The human prostatic epithelial cell line BPH-1 is normally nontumorigenic in nude mice. The present report demonstrates that this cell line can be permanently transformed by its microenvironment to become tumorigenic. The establishment of a series of tumorigenic sublines based on this parental cell line is described. BPH-1 cells were induced to form tumors either by recombination with human prostatic carcinoma-associated fibroblasts (CAFs) or by exposure to carcinogenic doses of testosterone and estradiol (T+E2) after recombination with rat urogenital sinus mesenchyme. Epithelial cells isolated from these tumors were established as cell strains in culture. When regrafted to nude mouse hosts epithelial cells isolated from CAF- or T+E2-induced tumors were found to be consistently tumorigenic even in the absence of CAF or T+E2. The T+E2-induced cell strains have been designated BPH1(TETD)-A and -B and the CAF-induced strains are designated BPH1(CAFTD)-01 through -08. In vitro, the cell...
Epithelial outgrowth from suspension cultures of human prostatic tissue
In Vitro, 1974
The primary objective of this study was to obtain pure cultures of prostatic epithelium. Encapsulation by epithelial cells and hypocellularity in stroma occurred when explants of prostatic tissue were maintained in suspension cultures. Twenty per cent fetal bovine serum incorporated into the medium provided optimal conditions for encapsulation and preservation of epithelial cell viability and architecture. Horse serum at the same concentration was less effective. When encapsulated explants were allowed to attach to the substrate, 10 and 20% horse serum favored growth of epithelial cells while fetal bovine serum also stimulated fibroblastic growth. Mechanisms for the induction of hypocellularity, encapsulation, squamous metaplasia and central necrosis in explants were studied. Relationship between the type and concentration of serum and the nature and extent of outgrowth are discussed.
Differentiation of rat neonatal ventral prostates grown in a serum‐free organ culture system
The Prostate, 1997
BACKGROUND. Organ culture methods have long been used in the study of the prostate because effects of drugs and hormones can be examined in the absence of systemic effects. METHODS. Neonatal rat ventral prostates (VP) were grown on Millipore filters floating on fluid medium composed of Dulbecco's modified Eagle's medium/Ham's F-12 supplemented with insulin, transferrin, and hydrocortisone, and in the presence or absence of testosterone (T, 10 −8 M). RESULTS. In the presence of T, ductal lumen formation occurred, ductal branching was extensive, and basal and luminal epithelial cells were identified by immunocytochemistry based on their distinctive cytokeratin profile. In the absence of T, ductal lumen formation did not occur, basal and luminal epithelial cells failed to differentiate, and there was a marked decrease in prostatic organ size relative to glands grown with T. Interestingly, DNA synthesis, as measured by counts per min (CPM) for 3 H-thymidine incorporation, showed that DNA synthesis per g DNA at 7 days of organ culture was not inhibited by lack of T. Androgen receptor expression is another marker of prostatic epithelial differentiation, and it occurred in both the presence and absence of T. CONCLUSIONS. Growth and differentiation of the neonatal rat prostate in vitro occur in a manner similar to that of the developing prostate in vivo, demonstrating that organ cultures of neonatal rat ventral prostates provide a faithful model for studying rat prostatic development and differentiation under serum-free conditions.
Characterization of canine prostatic cells from normal and hyperplastic glands
Molecular and Cellular Endocrinology, 1980
Secretory and non-secretory epithelial cells and fibroblasts obtained from normal and hyperplastic canine prostate glands and from prostates of 6-week castrated dogs are cultured in monolayers. Prostatic fibroblasts are grown in non-selective culture medium and found at densities of 1.040-1.045 g/ml in Percoll gradients. Enriched populations of each epi~e~~al cell type are obtained by varying the duration of the culture combined with the use of selective MEM D-Val mixture. When separated by centrifugation in Percoll density gradients, the secretory cells (high A.P.) are found at densities of 1.02-l .03 g/ml whereas the non-secretory cells (low A.P.) have densities of 1.05-1.06 g/ml. Both epithelial cell types are present in the normal and hyperplastic glands at the time of explantation. There is no correlation between the prostatic weight and the proportion of each cell type present in the tissue. On the basis of cell density in Percoll gradients and A.P. activity, those prostates with a high percentage of non-sccretory epithelial cells yield better attachment and overa cultures than glands consisting mainly of secretory cells. Our results strongly suggest that non-secretory cells are precursors of the secretory type. In addition, the cells involved in the aging process of the culture are the secretory epithelial cells.
Prostate Long-Term Epithelial Cell Lines. Biological and Biochemical Features
Annals of the New York Academy of Sciences, 1990
All the androgen'-sensitive peripheral tissues and cells, like prostate, kidney, sebaceous gland, and seminal vesicles, are commonly believed to possess the ability to metabolize testosterone (T). Two main pathways are well recognized. One is the conversion of T into dihydrotestosterone (DHT) and 3a-androstanediol (3a-diol) or 3p-androstanediol(3~-diol). This conversion, considered to be a prerequisite for the multiple actions exerted by T on target structures,I4 needs an enzymatic complex including Sa-reductase and two 3a-or 3p-hydroxysteroid dehydrogenases (HSD).1,5-9 The second possible pathway is the conversion of T into androstenedione (deltaCA), Sa-androstanedione (5a-A), and androsterone (A). This pathway has been ascertained in normal and diseased prostate gland of both doglo." and man,iz-ls but its presence in rat prostate is still debated.'.I6 In a previous report, Robe1 er ~1 .~ showed that explants of rat prostatic tissue do not form delta4-A from T. Controversially, Djoseland et a/.16 found that either delta4-A, Sa-A and A are present in the prostate of adult male rats after in vivo administration of T. In a recent work, Martini and coworkers produced clear evidence that the prostate of normal young rats is able to convert T into high levels of DHT and diols, but substantial amounts of delta4-A, 5aA, and A have also been detected. Moreover, data from several authors demonstrate that a This work has been partially supported by financial grants from the National Research e Systematic names, trivial names, and abbreviations used for androgens: 4-androsten-17P-ol-3-one1 testosterone (T); 5a-androstan-l7P-ol-3-one, dihydrotestosterone (DHT); Saandrostan-3a, 17p-dio1, 3cu-androstanediol (3a-diol); 5a-androstan-3P, 17P-dio1, 3P-androstanediol (3P-diol); 4-androsten-3,17-dione, androstenedione (delta4-A); Sa-androstan-3,17-dione, androstanedione (5a-A); 5a-androstan-3a-ol-17-one, androsterone (A); Sa-androstan-3p-01-17-one, Epiandrosterone (Epi-A).